From Abracadabra to Zombies

Book Review

"Cancer’s life is a recapitulation of the body’s life, its existence a pathological mirror of our own....Cancer is not merely a lump in the body; it is a disease that migrates, evolves, invades organs, destroys tissues, and resists drugs." --Siddhartha Mukherjee

In addition to telling the many riveting stories of those who have persevered in trying to identify the causes and cures of the many kinds of cancer that are inevitable (we now know) given our genetic nature, Mukherjee provides us with insight after insight into how scientists think. It is messy at times, wrong often enough, but in the end it is a delightful thing to see unfolding before our eyes. It is especially delightful to follow the progress of the disease and our understanding of it from the time of the ancient Egyptians to the present day. (Don't believe those who tell you there was no cancer in ancient times. Those who tell you cancer is a man-made disease are not telling you the truth.)

On the other side, reading about the desperate desire for a cure that leads many patients to demand access to treatments before they have been properly tested is a reminder that emotions, not logical thinking, is what often drives our most important beliefs and actions.

"Cancer, we now know, is a clonal disease. Nearly every known cancer originates from one ancestral cell that, having acquired the capacity of limitless cell division and survival, gives rise to limitless numbers of descendants....Cancer is an age-related disease—sometimes exponentially so. The risk of breast cancer, for instance, is about 1 in 400 for a thirty-year-old woman and increases to 1 in 9 for a seventy-year-old." Every gene in every cell in your body has the potential to mutate. Some of those mutations affect the genes that regulate cell division in ways that cause cancer. Finding just those mutations and developing ways to mitigate or eliminate their uncontrolled effects is the center of today's cancer research.

Among the many diverse pathways Mukherjee takes us down is one where he reviews the data on cancer mortality. There is good news and bad news. The good news is that "between 1990 and 2005, breast cancer mortality had dwindled an unprecedented 24 percent. Three interventions had potentially driven down the breast cancer death rate—mammography (screening to catch early breast cancer and thereby prevent invasive breast cancer), surgery, and adjuvant chemotherapy (chemotherapy after surgery to remove remnant cancer cells). Donald Berry, a statistician in Houston, Texas, set out to answer a controversial question: How much had mammography and chemotherapy independently contributed to survival? .... When Berry assessed the effect of each intervention independently using statistical models, it was a satisfying tie: both cancer prevention and chemotherapy had diminished breast cancer mortality equally—12 percent for mammography and 12 percent for chemotherapy...." (Compare this to the news that mammograms and self–breast exams do little to protect women under 50 against breast cancer.)

Other types of cancers are being treated with drugs that aren't just toxins that attack dividing cells indiscriminately. "In the decade since the discovery of Gleevec [imatinib], twenty-four novel drugs have been listed by the National Cancer Institute as cancer-targeted therapies. Dozens more are in development." The development of Gleevec [imatinib] is a testament to how far science has come in the quest to develop a cure for cancer. "Imatinib is the first member of a new class of agents that act by specifically inhibiting a certain enzyme that is characteristic of a particular cancer cell, rather than non-specifically inhibiting and killing all rapidly dividing cells...."* For those who think Big Pharma is out to kill us, the development of Gleevec and two dozen similar drugs should be a wake-up call. Someday chemotherapy, radiation, and radical surgery may be a thing of the past in cancer treatment. How we got to chemotherapy and specific genetic therapies from the ancient practices of bloodletting, cupping, leaching, and purging is an amazing story. Some day we will have a Cancer Genome Atlas that "will chart the entire territory of cancer: by sequencing the entire genome of several tumor types, every single mutated gene will be identified." That will open the door to the search for the harmful mutations and for specific agents to counteract them.

Many readers will find just as interesting Mukherjee's stories about the hypotheses and discoveries of carcinogenic substances from chimney dust to pickling preservatives, from tobacco to radiation.

Nineteenth-century doctors often linked cancer to civilization: cancer, they imagined, was caused by the rush and whirl of modern life, which somehow incited pathological growth in the body. The link was correct, but the causality was not: civilization did not cause cancer, but by extending human life spans—civilization unveiled it.

Longevity, although certainly the most important contributor to the prevalence of cancer in the early twentieth century, is probably not the only contributor. Our capacity to detect cancer earlier and earlier, and to attribute deaths accurately to it, has also dramatically increased in the last century. The death of a child with leukemia in the 1850s would have been attributed to an abscess or infection (or, as Bennett would have it, to a “suppuration of blood”). And surgery, biopsy, and autopsy techniques have further sharpened our ability to diagnose cancer. The introduction of mammography to detect breast cancer early in its course sharply increased its incidence—a seemingly paradoxical result that makes perfect sense when we realize that the X-rays allow earlier tumors to be diagnosed.

Finally, changes in the structure of modern life have radically shifted the spectrum of cancers—increasing the incidence of some, decreasing the incidence of others. Stomach cancer, for instance, was highly prevalent in certain populations until the late nineteenth century, likely the result of several carcinogens found in pickling reagents and preservatives and exacerbated by endemic and contagious infection with a bacterium that causes stomach cancer.

Equally interesting are the stories of the men and women who have been in the trenches in the so-called "war on cancer." Most of the stories are ennobling and a testament to perseverance, dedication, and passion. Some are disheartening. One is disgusting: the story of Dr. Werner Bezwoda of the University of Witwatersrand in Johannesburg, South Africa. Bezwoda raised hopes of a cure for breast cancer, the most prevalent of all cancers, by reporting at scientific meetings around the world of his tremendous success with bone-marrow transplantation and high-dose chemotherapy. When American researchers visited his lab to find out why they were failing where Bezwoda was succeeding, they discovered that he had very few records and that his data was non-existent. Confronted, Bezwoda admitted his fraud.

One thing that may surprise some readers is the prevalence of trial and error in the history of cancer research. Trial and error is a slow and primitive way to study something so complex, but is inevitable given the ethical prohibitions of doing randomized controlled studies where suspected carcinogens or potentially beneficial cancer treatments are introduced in an experimental group and compared to controls. A lot of guesswork went into the earliest forms of surgery and chemotherapy for cancer patients. Many people were guinea pigs. The adults may have been willing guinea pigs, but the children couldn't have had any idea what was being done to them. Looking back, this experimentation on humans--I can't think of a euphemism to describe what occurred--may have been inevitable and necessary, but that doesn't take away from the repulsion many will feel as they read of the treatment of leukemia in children in the early days.

The Emperor of All Maladies is informative, educational, entertaining, and the stories are as well told as the writing is eloquent. I found the book to be a page turner (or in my case a Kindle clicker) and I highly recommend it.